Reference

Combination therapy for depression, prevention of suicide, and various medical and psychiatric conditions

Combination therapy for depression, prevention of suicide, and various medical and psychiatric conditions. Migaly, Peter (USA ). PCT Int. Appl. WO 2004010932 A2 5 Feb 2004,28 pp. DESIGNATED STATES: W: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, OM, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, TJ, TM, TN, TR, TT, TZ, UA, UG, UZ, VC, VN, YU, ZA, ZM, ZW; RW: AT, BE, BF, BJ, CF, CG, CH, CI, CM, CY, DE, DK, ES, FI, FR, GA, GB, GR, IE, IT, LU, MC, ML, MR, NE, NL, PT, SE, SN, TD, TG, TR. (English). (World Intellectual Property Organization). CODEN: PIXXD2. CLASS: ICM: A61K. 71675-85-9 and 303-49-1 are cas registry numbers of chemicals which are used as reagents here. APPLICATION: WO 2003-US23326 25 Jul 2003. PRIORITY: US 2002-PV319436 30 Jul 2002. DOCUMENT TYPE: Patent CA Section: 1 (Pharmacology) Section cross-reference(s): 2, 4 The present invention relates to a new method of treatment for persons meeting diagnoses for major depressive disorder, or other unipolar (non-bipolar, nonpsychotic and non-treatment resistant) depression. The method comprises administering a combination of two categories of drugs, antipsychotics or dopamine system stabilizers, in combination with a newer antidepressant such as a selective serotonin reuptake inhibitor, as initial treatment or as soon as possible. The method targets the prevention of suicide, and provides other benefits including preventing disease progression development of tolerance toward the antidepressants. Another aspect of the invention relates to using the method for alleviating cognitive distortion and related functional impairment or health risks, and/or using the method for smoking cessation or nicotine withdrawal. .

The antinociceptive effect of amisulpride in mice is mediated through opioid mechanisms

The antinociceptive effect of amisulpride in mice is mediated through opioid mechanisms. Weizman, Tal; Pick, Chaim G.In this study，71675-85-9 is also used.; Backer, Maria M.; Rigai, Tova; Bloch, Miki; Schreiber, Shaul (Tel Aviv Sourasky Medical Center, Department of Psychiatry, Tel-Aviv University Sackler School of Medicine, Tel Aviv-Jaffa 64239, Israel). European Journal of Pharmacology, 478(2-3), 155-159 (English) 2003 Elsevier Science B.V. CODEN: EJPHAZ. ISSN: 0014-2999. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Antinociceptive effects of various neuroleptics in animal acute pain-models have been described, mediated trough different pathways including the opioid system. In this study, we assessed the antinociceptive effects of the atypical neuroleptic drug amisulpride, which acts as a selective blocker of dopamine D2 and D3 receptors. Furthermore, at low doses amisulpride has a selective preference for presynaptic dopamine autoreceptors, while at high doses it manifests a preferential action at post-synaptic dopamine receptors. We found amisulpride to be a potent antinociceptor agent in the mouse tail-flick assay, with an ED50 of 36.6 mg/kg. This effect was antagonized by naloxone (P<0.05), indicating an involvement of opioid mechanisms as mediators of the antinociceptive effect of amisulpride. b-Funaltrexamine (m1- and m2-opioid receptor antagonist), naloxonazine (selective m1-opioid receptor antagonist), naltrindole (selective d-opioid receptor antagonist), Nor-binaltorphamine (k1-opioid receptor antagonist) reversed amisulpride antinociception at the same dose that they antagonized morphine's antinociceptive effect (all P<0.005). We found that the sensitivity of amisulpride-induced antinociception is mediated through selective involvement of all three opioid receptor subtypes. Based on previous studies with risperidone, clozapine and olanzapine we tend to attribute this global interaction with the opioid system to amisulpride's action at the dopamine D2 receptor sites. .